Metabolic and genetic risk factors for migraine in children

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.     

Modifiable risk factors for migraine progression

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.     

Prothrombotic genetic risk factors in patients with coexisting migraine and ischemic cerebrovascular disease

The role of hemostatic elements in stroke has been clearly defined but several prothrombotic polymorphisms of hemostatic factors, important for other thromboembolic disorders, seem not to be very significant in stroke. Recently, the high prevalence of factor V Leiden in patients with stroke and a history of migraine has suggested an association between migraine and prothrombotic genetic risk factors. Stroke being a multifactorial disease, the aim of this study was to test whether prothrombotic tendencies increase the risk of stroke in patients with migraine. We determined the prevalence of four prothrombotic genetic risk factors (factor V R/Q 506, factor II 20210 G/A, decanucleotide insertion/deletion in the factor VII promoter, and the platelet HPA-1 alloantigen system) in 17 patients with coexisting ischemic cerebrovascular disease and migraine, 107 patients with ischemic cerebrovascular disease, 106 patients with migraine, and 202 control subjects. Genotyping for all polymorphisms analyzed in our study were performed after specific genomic polymerase chain reaction, and confirmed by single-strain conformation polymorphism analysis. In the group of patients with coexisting ischemic cerebrovascular disease and migraine, the prevalence of prothrombotic genotypes (factor V Leiden, 5.8%; factor II 20210 A, 0%; factor VII A1, 70.6%; and HPA-1b, 35.3%) was similar to that obtained in all other groups. We can conclude that the studied polymorphisms do not seem to be associated with the development of ischemic cerebrovascular disease in those patients with migraine.     

航天工作者偏头痛患病率及相关因素分析

目的:调查航天工作者的偏头痛患病率及临床特征,探讨航天工作者偏头痛的危险因素,并为偏头痛的防治提供有效策略。方法:采取分层随机整群抽样的方法,对1 200名航天工作者进行头痛问卷调查,问卷内容包括人口统计学资料、头痛诊断问题、睡眠质量。结果:136例符合偏头痛诊断标准,患病率为12.3%;先兆偏头痛52例(38.2%),无先兆偏头痛84例(61.8%);平均年龄(33±10.72)岁;男性46例(33.8%),女性90例(66.2%);大学以上学历占比最高(92.6%);疼痛部位为单侧86例(63.2%),搏动性62例(45.6%);发作时间为4～72 h 88例(64.7%);中重度112例(72.3%);伴随症状出现畏声64例(47.1%),恶心59例(43.3%);活动加重头痛86例(63.2%);诱发因素中睡眠缺乏99例(72.8%)。单因素分析显示,不同性别、职业类型、睡眠质量组间偏头痛的分布存在统计学差异(P<0.05)。多因素Logistic回归分析显示,女性、睡眠质量差者患偏头痛的风险较高(P<0.05)。结论:航天工作者偏头痛患病率较高,性别(女)和睡眠障碍是其主要危险因素。     

Genes and atherosclerosis: at the origin of the predisposition

Atherosclerosis (ATS) is a multifactorial disease caused by the interaction of established or emerging risk factors with multiple predisposing genes that regulate ATS-related processes. This review will discuss the current knowledge concerning the potential role of the genetic variations that could promote and/or accelerate ATS, in both animal models and humans. Allelic polymorphisms or variations of distinct genes that enhance the risk of ATS frequently occur in the general population, but only adequate gene-environment interactions will lead to the disease. The main genes so far studied are involved in the regulation of processes such as endothelial function, antioxidant potential, coagulation, inflammatory response, and lipid, protein and carbohydrate metabolism. The detection of candidate genes associated with ATS could allow, in the near future, earlier interventions in genetically susceptible individuals. Further, large-scale population studies are needed to obtain more information on the specific gene-environment and drug-gene interactions capable of influencing ATS progression.     

Histamine-N-methyl transferase polymorphism and risk for migraine

Background/Objectives.— Histamine has been implicated in the pathogenesis of migraine. In the CNS, histamine is almost exclusively metabolized by the polymorphic enzyme histamine N‐methyltransferase (HNMT). The HNMT gene (chromosome 2q22.1), shows diverse single nucleotide polymorphisms. One of these, located in exon 4 C314T, causes the amino acid substitution Thr105Ile, related to decreased enzyme activity. The aim of this study was to investigate the possible association between HNMT polymorphism and the risk for migraine. Methods.— We studied the frequency of the HNMT genotypes and allelic variantes in 197 patients with migraine and 245 healthy controls using a PCR‐RLFP method. Results.— The frequencies of the HNMT genotypes and allelic variants did not differ significantly between migraine patients and controls, and were unrelated with the age of onset of migraine attacks, gender, personal history of allergic diseases, family history of migraine, or presence of aura. Conclusion.— The results of the present study suggest that HNMT polymorphism in not related with the risk for migraine.     

Cardiac risk factors and the use of triptans: a survey study

OBJECTIVE: To describe current practice in triptan use. BACKGROUND: Triptans are effective migraine treatments that cause chest symptoms in some patients. True cardiac ischemia is rare. Design.-Headache specialists and family practitioners completed questionnaires regarding the times when triptans are contraindicated, obtaining electrocardiograms (ECGs), and giving the first dose in the office. RESULTS: Sixty-five headache specialists and 67 family practitioners responded. Headache specialists saw an average of 36.3 patients with headache per week. Family practitioners saw an average of 7.2. Family practitioners and headache specialists had similar opinions regarding the age at which triptans were contraindicated with various numbers of risk factors. Sixty-one percent of headache specialists and 50% of family practitioners would not use a triptan at any age for patients with more than three risk factors (P = NS). Ten percent of headache specialists obtained an ECG for all patients being prescribed triptans, while no family practitioners did (P =. 008). Ten percent of both family practitioners and headache specialists never obtained an ECG, even with multiple cardiac risk factors. Headache specialists obtained ECGs more often than family practitioners (P <.002 for one to three risk factors). Family practitioners were more likely to give the first dose of the triptan in the office regardless of cardiovascular risk (58% versus 20%, P <. 001). Forty-five percent of headache specialists and 2% of family practitioners never gave the first dose in the office (P <.001). Family practitioners gave the first dose in the office more readily than headache specialists in patients with no risk factors (P =.001), but not for one or more risk factors. CONCLUSIONS: No consensus exists among family practitioners or headache specialists about when to avoid using a triptan due to excessive cardiac risk factors, when to obtain an ECG prior to using a triptan, and when to give the first dose of a triptan in the office. Headache specialists are more likely to obtain ECGs, whereas family practitioners are more likely to give the first dose of a triptan in the office.     

Possible risk factors and precipitants for migraine with aura in discordant twin-pairs: a population-based study

The aim of the present study was to detect possible risk factors in migraine with aura (MA) by analysis of discordant twin-pairs. In a recent population-based twin study we established that environmental factors account for approximately 50% of the variation in liability to MA. A cohort of 5,360 same-gender twin-pairs from the general population was screened for migraine. All twin-pairs with possible migraine were interviewed by a physician. A questionnaire provided information about living conditions and lifestyle. Of the 169 discordant twin-pairs 51 were monozygotic and 118 were dizygotic twin-pairs. Several putative risk factors-schooling, education, marital status, smoking status and alcohol consumption-showed no association with MA. The presence of migraine without aura or tension-type headache did not increase the risk of MA. Stress and mental tension, and bright light precipitated attacks of MA in, respectively, 44% and 28% of the twins.     

Migraine trigger factors in a non-clinical Mexican-American population in San Diego county: implications for etiology

We conducted an investigation of migraine headache in a general population of Mexican-Americans living in San Diego county. Specific headache triggers were reported and analyzed, the most frequently reported for females with migraine being missing meals (58.9%), weather changes (54.4%), menstruation (53.6%), post-crisis letdown (52.7%), and fatigue (51.8%). The most frequently reported trigger factors for migraines reported by males were fatigue (58.8%), sleep (as a precipitating factor) (56.3%), post-crisis letdown (41.2%), and weather changes (37.5%). Trigger factors were further evaluated using stratification by presence or absence of Raynaud's phenomenon (RP), menstrual migraine, family history of migraine, and by migraine type. Odds ratios and 95% confidence intervals were calculated. These results suggest that subjects with migraine and RP (perhaps indicative of a systematic vascular tone disorder) and those with menstrual migraine (indicative of sensitivity to hormonal changes) may overall be more sensitive to certain environmental stimuli, particularly those involving change in the internal environment.     

Modifiable Risk Factors for Migraine Progression (or for Chronic Daily Headaches)—Clinical Lessons

Herein we summarize clinical issues gleaned from a full peer-reviewed article on modifiable risk factors for migraine. Since migraine is progressive in some but not in most individuals, identifying patients at risk for progression is crucial. Key interventions include: (1) Decrease headache frequency with behavioral and pharmacologic interventions; (2) Monitor the body mass index and encourage maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and treat depression and other psychiatric comorbidities. These recommendations have not been demonstrated to improve outcomes in longitudinal studies.     

Chronic headache and potentially modifiable risk factors: screening and behavioral management of sleep disorders

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.     

Migraine and genetic and acquired vasculopathies

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.     

Migraine and the hypothalamus

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.     

Migraine to the year 2000

Although migraine is inextricably bound up with 5-hydroxytryptamine and its many receptors, its precise mechanisms continue to elude us and there is still no clear evidence supporting either a vascular or neurogenic hypothesis unequivocally. What appears to distinguish migraine sufferers from normal subjects may be a greater genetic sensitivity to a wide variety of triggering agents-even including nitric oxide and the migraine aura, as well as those more usually recognized. Attention is drawn to a possible role for neurotrophins, such as the hyperalgesia-provoking nerve growth factor (NGF) in particular, as well as basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF).     

Migraine: Epidemiology, Impact, and Risk Factors for Progression

Migraine is a chronic and sometimes progressive disorder characterized by recurrent episodes of headache and associated symptoms. This article reviews the epidemiology of and the risk factors for migraine described in population studies, and discusses the burden of disease and the socioeconomic costs of migraine. In the years prior to puberty, migraine is more common among boys than girls. By the onset of puberty, migraine is more prevalent in girls, and by the late teens, females are about twice as likely to suffer from migraine as males. The prevalence of migraine peaks in both sexes during the most productive years of adulthood (age 25 to 55 years) and, in the United States, the prevalence is higher in individuals of lower socioeconomic status. Direct costs of migraine include the cost of migraine medications and health care expenses. Indirect costs associated with migraine include reduced productivity due to absenteeism and reduced performance while at work. Recent evidence suggests that a subgroup of migraine patients may have a clinically progressive disorder. Future epidemiologic studies should focus on identifying patients who are at higher risk for progression and on assessing the impact of intervention strategies on disease progression.     

Thrombophilic risk factors in patients with severe carotid atherosclerosis.

Carotid stenosis and atrial fibrillation are the strongest risk factors for ischemic stroke. Ongoing prevention efforts include the identification of novel factors that increase the risk for carotid atherosclerosis. The aim of this study was to determine the thrombophilic risk profile of patients with severe carotid stenosis by evaluating a number of genetic and metabolic risk factors [factor (F)II G20210A, factor V Leiden, MTHFR C677T polymorphisms, anticardiolipin antibodies (aCL), lipoprotein(a) (Lp(a)), and homocysteine (Hcy)]. The study population consisted of 615 patients [(410 M/205 F; median age 73 (26-94) years] with severe (> 70%) carotid stenosis, and 615 apparently healthy subjects [(410 M/205 F; age 73 (31-92) years]. On multivariate analysis, independent risk factors were elevated Hcy [odds ratio (OR) 7.6, 95% confidence interval (CI) 4.8, 11.8] and Lp(a) levels (OR 2.9, 95% CI 2.1, 3.9), the presence of aCL (OR 5.7, 95% CI 3.1, 10.4) and heterozygosity for FII G20210A polymorphism (OR 2.8, 95% CI 1.3, 5.9). In the subgroup of women, independent risk factors for severe carotid atherosclerosis were: high levels of Hcy and Lp(a) and the presence of aCL, whereas hyperhomocysteinemia, elevated Lp(a) levels, aCL, FII G20210A and MTHFR 677TT polymorphisms remained independent risk factors in the subgroup of men. The results of the present study demonstrate that the prevalence of the thrombophilic risk factors is increased in patients with severe carotid atherosclerosis.     

Risk factors for gastroesophageal reflux disease and analysis of genetic contributors

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett’s esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett’s esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.